Microbes in Your Mouth

A tale of slime cities

08-01-2001
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Elia Ben-Ari

Run your tongue over your teeth. Do you detect something more than a just-brushed, slick surface, something maybe just a little slimy? If so, you´ve just felt a biofilm, a highly organized community of microbes with its own food delivery, waste disposal, communication and defense systems. Not just on teeth, but wherever water, nutrients and a solid surface are available, bacteria and other microbes are likely to put down stakes and form these sticky, slimy structures.

Just two decades ago, most biologists had no idea that microbes prefer living in "cities" of billions to the solitary, free-floating state. "We´d known forever that biofilms existed," says University of Iowa microbiologist Peter Greenberg. "The big advance was learning that they are a major bacterial life-style."

Some biofilms are beneficial. They break down contaminants in water and soil and can form protective coatings that block the growth of disease-causing microbes on the surface of tissues. But mounting evidence suggests that these teeming microbial metropolises also are responsible for many chronic human infections that are difficult—even impossible—to eradicate. Biofilms cause trouble in industrial settings, too, where they clog oil pipelines and water filtration systems, contaminate food-processing equipment and foul the surfaces of computer chips. Altogether, biofilm-related problems cost the United States billions of dollars each year.

To an individual microbe, the biofilm life-style offers many advantages. It provides a safe haven from hostile environments and potential predators, as well as a stable location near a dependable food source. Microbial residents also are protected from assaults by the body´s immune system and from antibiotics and chemical disinfectants.

A biofilm may be composed of a single bacterial species or a mixture of anywhere from two to several hundred kinds of bacteria, plus fungi, algae and other microbes. Together these organisms form a highly cooperative community in which each member performs a specialized job. The community has a distinct architecture, consisting of towers of microbes with water channels running among them. Like a primitive circulatory system, the channels let nutrients flow in and waste products flow out. The entire structure is embedded in a slimy web of molecules produced by cells in the biofilm itself. This sticky substrate glues the film to a surface and holds the entire microbial city together.

Dental researchers were the first to realize the role of biofilms in causing disease: Dental plaque (biofilm on teeth) can cause cavities and periodontal disease if not kept in check by regular brushing and flossing. Other chronic infections now known to be caused by biofilms include heart valve and prostate infections, the recurring lung infections that ultimately devastate most people with cystic fibrosis and the chronic middle-ear infections that plague many children.

Biofilms also flourish on nonliving surfaces implanted in the body, such as catheters, artificial joints and dental implants. "Once you establish a biofilm infection on an implanted device it´s very difficult to eradicate," says Phil Stewart, a chemical engineer at Montana State University´s Center for Biofilm Engineering. Often the only option is surgical removal of the infected device.

Because community life gives microbial inhabitants protection from their enemies—through biological mechanisms that remain largely unknown—researchers estimate that bacteria in biofilms are between 100 and 1,000 times more resistant to antibiotics than their free-floating counterparts. Doctors generally treat biofilm infections with the strongest antibiotics they can get their hands on. Such treatments may reduce symptoms and damp down the disease, but they rarely eliminate it. Eventually the microbes bounce back, and symptoms recur. In some cases, free-floating microbes released from a biofilm trigger a more serious, fast-growing infection. Although antibiotics can usually eliminate these acute infections, the biofilm that spawned them will remain, threatening to repeat the cycle.

"It´s only been in the last couple of years that microbiologists have appreciated that biofilms are a major cause of persistent infection," says Greenberg. The realization has stimulated interest among researchers and biotechnology companies, which are working to develop more effective treatments. By studying the details of how microbial cities form, and what makes cells in a biofilm different from free-floating cells, researchers hope to find clues to new therapies.

One such clue has come from the discovery of chemical signals that bacteria use to "talk" to one another during the carefully orchestrated process of building a biofilm. A 1998 study by Greenberg and his colleagues showed that mutant bacteria that were unable to make one signaling molecule could not form normal biofilms. He and other researchers are teaming up with biotech companies to look for chemical compounds that would interfere with these microbial communication systems.

"It´s probably easier to prevent a biofilm from forming than to destroy a preexisting one," says Harvard University microbiologist Roberto Kolter. "But you may not want to administer a drug to every patient who might get a biofilm infection." Ideally, Kolter and Greenberg say, researchers need to develop drugs that can disrupt mature biofilms.

In one promising study, researchers at the Center for Biofilm Engineering have shown that zapping a microbial city with a weak electrical current can enhance the ability of antibiotics to kill biofilms grown in the laboratory. Ultrasound, too, can help antibiotics wipe out communal-living bacteria more effectively.

To tackle biofilms that grow on implanted devices, researchers are developing and testing materials they hope will stop or slow down microbes in the process of constructing slime cities. Among the most promising so far are materials impregnated with antibiotics. "The Holy Grail of biofilm control is an anti-fouling surface—the Teflon of biofilm formation—that organisms simply don´t stick to," says Stewart.

Creating such "stealth" materials presents a major challenge, though, says Stewart. As for when drugs to eradicate biofilms will be available, Greenberg hopes that the search will take no more than five to ten years. Yet microbes, as the most ancient, abundant and adaptable life forms on Earth, may ultimately get around all such barriers. "If we´ve learned anything," says Kolter, "it´s that bacteria are very versatile. If one avenue to biofilm formation is blocked, microbes are likely to find another route."